Search

Pronounced temporal and spatial variation in the availability of food resources can produce energetic deficits in organisms. Fruit-dependent Bornean orangutans face extreme variation in fruit availability and experience negative energy and protein balance during episodes of fruit scarcity. We evaluate the possibility that orangutans of different sexes and ages catabolize muscle tissue when the availability of fruit is low. We assess variation in muscle mass by examining the relationship between urinary creatinine and specific gravity and use the residuals as a non-invasive measure of estimated lean body mass (ELBM). Despite orangutans having a suite of adaptations to buffer them from fruit scarcity and associated caloric deficits, ELBM was lower during low fruit periods in all age-sex classes. As predicted, adult male orangutans had higher ELBM than adult females and immatures. Contrary to expectation, flanged and unflanged males did not differ significantly in ELBM. These findings highlight the precarity of orangutan health in the face of rapid environmental change and add to a growing body of evidence that orangutans are characterized by unique metabolic traits shaped by their unpredictable forest environment.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P −5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10−8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10−7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.